Protective Effect of Compound Tongluo Decoction on Brain Vascular Endothelial Cells after Ischemia-Reperfusion by Inhibition of Ferroptosis Through Regulating Nrf2/ARE/SLC7A11 Signaling Pathway.

Cerebral infarction is one of the most common diseases for aged people. Compound Tongluo Decoction (CTLD), a classic traditional Chinese Medicine prescription, has been widely used in the treatment of ischemic cerebral infarction. Transient middle cerebral artery occlusion (tMCAO) rat model is established for the animal experiment and oxygen-glucose deprivation and reperfusion (OGD/R) human umbilical vein endothelial cells (HUVECs) model are established for the cell experiment. This also use Nrf2-/- rats to detect the role of nuclear factor erythroid 2-related factor 2 (Nrf2). Longa score, Evans blue staining, brain water content measurement, and histological observation are done. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and other ferroptosis-related components are detected respectively. In the vivo experiment, CTLD relieved ischemia-reperfusion (IR) injury symptoms and attenuated IR injury in brain tissues of tMCAO rats by relieving peroxidation injury in brain tissues and inhibiting ferroptosis in tMCAO rats. Moreover, CTLD reversed OGD/R-induced oxidative damage of endothelial cells via suppressing ferroptosis. After knocking out the Nrf2 gene, the protective effect of CTLD is sharply reduced. This study put forward that CTLD can inhibit ferroptosis in I/R-injured vascular endothelium by regulating Nrf2/ARE/SLC7A11 signaling to improve the relative symptoms of rats after cerebral I/R injury, thus providing a viable treatment option for cerebrovascular disease.

Compound Tongluo Decoction inhibits endoplasmic reticulum stress-induced ferroptosis and promoted angiogenesis by activating the Sonic Hedgehog pathway in cerebral infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral infarction is one of the most common types of cerebrovascular diseases that threaten people's health. Compound Tongluo Decoction (CTLD), a traditional Chinese medicine formula, has various pharmacological activities, including the alleviation of cerebral infarction symptoms. AIM OF THE STUDY: This study aims to explore the potential mechanism by which CTLD alleviates cerebral infarction. MATERIAL AND METHODS: Middle cerebral artery occlusion (MCAO) rat model and oxygen-glucose deprivation and reperfusion (OGD/R) cell model were established for research. The expression of proteins related to endoplasmic reticulum (ER) stress, ferroptosis, Sonic Hedgehog (SHH) pathway and angiogenesis was analyzed by Western blot analysis. The expression of CD31 was detected by immunofluorescence to investigate angiogenesis. In addition, the expression of GRP78 and XBP-1 in brain tissues was investigated by immunohistochemistry. With the application of Prussian blue staining, iron deposition in brain tissue was detected. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) were detected using ELISA kits. The angiogenesis was analyzed by tube formation assay. RESULTS: The results presented in this research showed that CTLD and 4-phenyl butyric acid (4-PBA; the inhibitor of ER stress) could alleviate cerebral infarction. Mechanistically, CTLD and 4-PBA rescued ER stress and ferroptosis, but promoted SHH signaling in rats with cerebral infarction. In addition, cerebral infarction exhibited a high level of angiogenesis, which was aggravated by CTLD but suppressed by 4-PBA. Furthermore, CTLD inhibited ER stress and ferroptosis, but promoted SHH signaling and angiogenesis in OGD/R-induced PC12 cells, which was partly abolished by SANT-1, an antagonist of SHH signaling. CONCLUSION: In conclusion, this study revealed that CTLD might inhibit ferroptosis induced by endoplasmic reticulum stress and promote angiogenesis by activating the Sonic Hedgehog pathway in rats with cerebral infarction.

Predictors of poor glycemic control among type 2 diabetes mellitus patients treated with antidiabetic medications: A cross-sectional study in China.

ABSTRACT: This study aimed to clarify of the predictors of poor glycemic control in type 2 diabetes mellitus (T2DM) patients treated with antidiabetic medications in China.This study was a retrospective, cross-sectional study based on SuValue database. T2DM patients aged 18 years or older performing glycosylated hemoglobin A1c (HbA1c) examinations from January 1st, 2018 to December 31st, 2018 were included and have been treated with antidiabetic medications for at least 6 months. HbA1c < 7.0% was defined as adequate glycemic control. Multivariate analysis was performed for the factors associated with poor glycemic control.A total of 13972 T2DM patients were included in this study. The adequate glycemic control rate was 44.04% (n = 6153). In the multivariate analysis, predictors of poor glycemic control include longer T2DM duration (5-10 years vs <5 years and >10 years vs <5 years, odds ratio [OR] = 1.499 and 1.581, P < .001 and P = .008), myocardial infarction (OR = 1.141, P = .041), diabetic neuropathy (OR = 1.409, P < .001), secondary hospital (OR = 1.877, P < .001), underdeveloped regions (OR = 1.786, P < .001), insulin only (OR = 3.912, P < .001), combination of oral antidiabetic agents and/or insulin use (P < .001).In conclusion, longer T2DM duration, secondary hospital, myocardial infarction, diabetic neuropathy, undeveloped regions and use of polypharmacy and insulin were associated with poor glycemic control among T2DM patients treated with antidiabetic medications. Patient education and training of health care providers may be short-term strategy to achieve adequate glycemic control.

A pilot study on the epidemiology of hyperuricemia in Chinese adult population based on big data from Electronic Medical Records 2014 to 2018.

BACKGROUND: We performed this study based on big data from Electronic Medical Records (EMR) of outpatients and inpatients from 52 hospitals in China to investigate the prevalence of hyperuricemia in Chinese adults. METHODS: In this retrospective, descriptive study, a total of 3,363,016 subjects from 52 hospitals in 13 provinces and municipalities in China were enrolled. Eligible subjects were 18 years and older performing serum uric acid test between 2014 and 2018. Subjects were divided into the total group (including the subjects from all the clinic departments) and department-amended group (including the subjects from all the departments except endocrinology, orthopedics, and rheumatology and immunology departments). RESULTS: The prevalence of hyperuricemia in the department-amended group was lower than that in the total group (23.06% and 23.42% in 2018, respectively; P<0.0001). From 2014 to 2017, the prevalence of hyperuricemia increased year by year (18.29%, 20.02%, 20.16% and 23.06%, respectively) in the department-amended group. Besides, the prevalence of hyperuricemia was higher in men than that in women (38.00% and 11.89%, respectively; P<0.0001) and higher in southern region than in northern region (25.84% and 9.79%, respectively; P<0.0001) in department-amended group in 2018. CONCLUSIONS: Projections from our study estimate that about 271 million Chinese adults aged 18 years and older may have had hyperuricemia in 2018. These findings will be useful for the future researches and healthcare decision.

Incidence of constipation in stroke patients: A systematic review and meta-analysis.

There is growing awareness of a link between the gut and cardiovascular disease. Constipation is common among individuals who have had a stroke, and it negatively affects social functioning and quality of life. However, no systematic study on the incidence of constipation in stroke patients has been reported.We selected studies included in Medline, Embase, Cochrane database, and Web of Science. Studies were included if they reported the incidence in stroke patients. Two authors selected the studies, extracted the data independently, and assessed these. Subgroup analyses were conducted according to the stroke subtype and stage of stroke.After detailed evaluations, 8 studies (n  =  1385 participants) were found that contained data that were suitable for meta-analytic synthesis. A forest plot showed that the incidence of constipation was 48% (95% confidence interval [CI]  =  33%-63%). In the analysis of the type of stroke subgroup, the incidence of constipation in patients who had had a hemorrhagic stroke (66% [95% CI  =  40-91%]) was higher than that in patients who had experienced an ischemic stroke (51% [95% CI  =  27%-75%]). The incidence in the acute stage (45% [95% CI  =  36%-54%]) was lower than that in the rehabilitation stage (48% [95% CI  =  23%-73%]).Constipation after a stroke event occurs frequently. This finding may raise awareness about bowel complications to allow correct evaluation and proper management.

Panaxatriol saponins promotes angiogenesis and enhances cerebral perfusion after ischemic stroke in rats.

BACKGROUND: Panaxatriol saponins (PTS), an extract from the traditional Chinese herb Panax notoginseng, which has been used to treat ischemic stroke for many years in China. However, the mechanism underlying the effects of PTS remains unclear. This study aimed to determine whether PTS can protect against ischemic brain injury by promoting angiogenesis and to explore the possible mechanism by which it promotes angiogenesis. METHODS: Middle cerebral artery occlusion (MCAO) was induced in rats, and neurological deficit scores and brain infarct volumes were assessed. Micro-Positron emission tomography (PET) was adopted to assess cerebral perfusion, and real-time PCR and western blotting were used to evaluate vascular growth factor and Sonic hedgehog (Shh) pathway component levels. Immunofluorescence staining was used to determine capillary densities in ischemic penumbrae. RESULTS: We showed that PTS improved neurological function and reduced infarct volumes in MCAO rats. Micro-PET indicated that PTS can significantly increase 18F-fluorodeoxyglucose (18F-PDG) uptake by ischemic brain tissue and enhance cerebral perfusion after MCAO surgery. Moreover, PTS was able to increase capillary densities and enhance angiogenesis in ischemic boundary zones and up-regulate vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1) expression by activating the Shh signaling pathway. CONCLUSION: These findings indicate that PTS exerts protective effects against cerebral ischemic injury by enhancing angiogenesis and improving microperfusion.

[Effects of Tongnao Huoluo acupuncture therapy on Caspase-3 and Bcl-2 of rats with acute cerebral infarction].

OBJECTIVE: To evaluate effects of Tongnao Huoluo acupuncture therapy (THAT) on Bcl-2 and Caspase-3 rats with acute cerebral infarction (ACI). METHODS: Totally 264 SD rats were randomly divided into 5 groups, i.e. the THAT group (n =72), the thrombolysis group (n =72), the body acupuncture group (n =72), the ischemia control group (n =24), and the sham-operation group (n =24). Successfully modeled rats were recruited in all groups except the sham-operation group. Rats in the THAT group, the thrombolysis group, and the body acupuncture group were divided into 3 subgroups according to the disease occurrence time, i.e., < or = 1.5 h THAT group, 1.5+ -2 h THAT group, and 2+ -3 h THAT group. The neuroethological scores were assessed at 6, 24, and 72 h after treatment. The expressions of Bcl-2 and Caspase-3 were detected using immunohistochemical staining at 24 and 72 h respectively. RESULTS: In aspect of improving scores of neurological functions: At 6 h after treatment within 2 h after the disease occurrence, the neuroethological scores were lowered more obviously in the thrombolysis group than in the THAT group (P <0.05). There was statistical difference at 24 and 72 h within 2 - 3 h after the,disease occurrence between the THAT group and the thrombolysis group (P <0.05). Compared with before treatment, there was statistical difference at 24 and 72 h within 3 h after the disease occurrence (P <0. 05, P <0.01). In aspect of lowering the expression of Caspase-3 and elevating the expression of Bcl-2: There was statistical difference in lowering the expression of Caspase-3 and elevating the expression of Bcl-2 between the THAT group and the thrombolysis group at 72 h within 2 -3 after the disease occurrence (P <0.05, P < 0.01). CONCLUSION: THAT showed favorable effects in lowering neuroethological scores, lowering expression of Caspase-3, and elevating the expression of Bcl-2 of ACI rats.

Septoplasty and decongestant improve distribution of nasal spray.

This study prospectively examined the intranasal distribution of nasal spray after nasal septal correction and decongestant administration. A cohort of 20 patients was assessed for the distribution of nasal spray before and after nasal septum surgery. Sprays were dyed and administered one puff per nostril when patients hold their head up in an upright position. Before and after decongestant administration, the intranasal distribution was semi-quantitatively determined by nasal endoscopy. The results showed that the dyed drug was preferentially sprayed onto the nasal vestibule, the head of the inferior turbinate, the anterior part of septum and nasal floor. As far as the anterior-inferior segment of the nasal cavity was concerned, the distribution was found to be influenced neither by the decongestant nor by the surgery (P>0.05). However, both the decongestant and surgery expanded the distribution to the anatomical structures in the superior and posterior nasal cavity such as olfactory fissure, middle turbinate head and middle nasal meatus. No distribution was observed in the sphenoethmoidal recess, posterior septum, tail of inferior turbinate and nasopharynx. It was concluded that nasal septum surgery and decongestant administration significantly improves nasal spray distribution in the nasal cavity.

Septoplasty and Decongestant Improve Distribution of Nasal Spray / 华中科技大学学报（医学）（英德文版）

This study prospectively examined the intranasal distribution of nasal spray after nasal septal correction and decongestant administration.A cohort of 20 patients was assessed for the distribution of nasal spray before and after nasal septum surgery.Sprays were dyed and administered one puff per nostril when patients hold their head up in an upright position.Before and after decongestant administration,the intranasal distribution was semi-quantitatively determined by nasal endoscopy.The results showed that the dyed drug was preferentially sprayed onto the nasal vestibule,the head of the inferior turbinate,the anterior part of septum and nasal floor.As far as the anterior-inferior segment of the nasal cavity was concerned,the distribution was found to be influenced neither by the decongestant nor by the surgery (P＞0.05).However,both the decongestant and surgery expanded the distribution to the anatomical structures in the superior and posterior nasal cavity such as olfactory fissure,middle turbinate head and middle nasal meatus.No distribution was observed in the sphenoethmoidal recess,posterior septum,tail of inferior turbinate and nasopharynx.It was concluded that nasal septum surgery and decongestant administration significantly improves nasal spray distribution in the nasal cavity.

[Systematic reviews on efficacy and safety of beclomethasone nasal spray in the treatment of chronic adenoid hypertrophy in children].

OBJECTIVE: To systematically review the efficacy and safety of beclomethasone nasal spray in the treatment of chronic adenoid hypertrophy in children. METHODS: We computerized searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (issue1, 009), MEDLINE (1950 to August 2008), EMbase (1984 to August 2008), CNKI (1994 to September 2008), and VIP (1989 to August 2008), WANFANG DATA, Annual Review-s and Elsevier Science. Also the reference lists of all papers were identified for further trials. All searches were initially performed in May 2007 and updated in April 2009.Randomized controlled trials (RCT) and quasi-RCTs were identified and analyzed according to the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Three RCT were included. Meta-analysis was not performed due to heterogeneity and the data were summarized in a narrative format. The trials showed that higher doses of beclomethasone (336 microg/d, 400 microg/d) might improve the nasal obstruction symptoms and reduce adenoid size in children with adenoid hypertrophy. CONCLUSIONS: Higher and subsequently half doses of beclomethasone (336 microg/d, 400 microg/d) can improve the nasal obstruction symptoms in children with adenoid hypertrophy.The improvement appears to be associated with a reduction of adenoid size. Because of a lack of the RCT, further studies are required to support the use of beclomethasone as a first-line approach for these children.

[Effects of nasal septum operation combined with naso sinus on prognosis of nasal septum surgery].

OBJECTIVES: To investigate the effet of nasal septum operation combined with nasal sinuses on postoperative nasal septum. METHOD: Sixty-five patients with deflection of nasal septum complicating chronic sinusitis were underwent nasal septum and nasal sinus operations under nasal endoscope. Postoperative nasal septum recover were observed and compared with patients underwent only simple nasal septum operation. RESULT: Patients underwent nasal septum operations combined with nasal sinus, postoperative symptoms were more serious at early than simple nasal septum operations. At 3 months after operation, satisfactory degree of the former group were higher than the latter, and the former group didn't have complications such as nasal septum infection. CONCLUSION: Nasal septum operations combined with nasal sinus have no harmful effect on the prognosis of nasal septum, so it was safe and reliable.

[Treatment of traumatic pseudoaneurysm through completely embolizing siphon section of internal carotid artery].

OBJECTIVE: Pseudoaneurysm in siphon section of internal carotid artery (ICA) caused by craniocerebral trauma was diagnosed and totally embolized by applying digital subtraction angiography (DSA) technique, with satisfactory results. The clinical application of this technique was discussed. METHODS: The patients suffered from craniocerebral trauma with serious epistaxis were managed in our hospital by DSA. The patients with pseudoaneurysm in ICA were chosen from them. The circular function of Willis circulus in these patients were checked. If it was good, the ICA was totally embolised. RESULTS: Among 32 patients suffered from craniocerebral trauma with serious epistaxis, 6 patients were definitely diagnosed by DSA to have pseudoaneurysm. The embolism was performed in 5 of them. Among these 5 patients, 4 cured, and 1 died. The patient who could not be embolized also died. CONCLUSION: The pseudoaneurysm definitely diagnosed by DSA can be treated by embolizing siphon section of internal carotid artery completely, after checking the compensatory function of side branches in Willis circulus.

Influence of intranasal medication on the structure of the nasal mucosa.

OBJECTIVE: To study the influence of intranasal medication on the structure, pathology and reversibility of the nasal mucosa to provide a basis for the feasibility of intranasal route of drug administration. METHODS: Nasal drops of gentamicin were placed in the nasal cavity of rabbits for 3, 5, 7, 14 and 28 days. After that, the drops were stopped and drugs protecting the nasomucosa were used for one and three weeks. After being sacrificed over time, the nasomucosa of the rabbit was observed under optical and electron microscopes. RESULTS: Damage to the nasal mucosa appeared to different extents with prolonged use of nasal drops. Within 3 - 7 days of applying the drug, damages to the nasal mucosa gradually appeared, and after two and four weeks, were most serious. After stopping the drug, the nasal mucosa was gradually restored. CONCLUSION: Damages of drugs to the nasal mucosa could be restored. The intranasal route of drug administration would be feasible and clinically applicable.